Interferon (IFN) which is a member of cytokines shows antiviral activity, suppresses cell proliferation and regulates natural immune response. Interferon-beta (IFN-β) is a spherical protein having 5 helices and has a molecular weight of 22 kDa which becomes 18 kDa when removed its sugar chain (Arduini et al., Protein Science 8: pp 1867-1877, 1999).
Interferon-beta has been actively studied for its clinical applications, and in particular, it has been in the spotlight as a relieving, alleviating or treating agent for multiple sclerosis symptom (Goodkin et al., Multiple sclerosis: Treatment options for patients with relapsing-remitting and secondary progressive multiple sclerosis, 1999).
Besides multiple sclerosis, it has been reported that interferon-beta shows diverse immunological activities such as antiviral activity, cell growth inhibition or anti-growth activity, increasing lymphocytotoxicity, immunoregulatory activity, inducing or suppressing proliferation of target cells, activating macrophages, increasing cytokine production, increasing cytotoxicity T cell effect, increasing natural killer cells, and therefore, it is effectively used for treating cancer, auto-immune disorders, viral infections, HIV-relating diseases, hepatitis C, rheumatoid arthritis and the like (Pilling et al., European Journal of Immunology 29: pp 1041-1050, 1999, Young et al., Neurology 51: pp 682-689, 1998; Cirelli et al., Major therapeutic uses of interferons. Clin Immunother 3: pp 27-87, 1995).
Human interferon-beta is a kind of glycoproteins linked to one or more sugar chains, and such sugar chain plays an important role in the glycoprotein's activity.
Therefore, there is an instance where a glycoprotein's activity becomes increased when a sugar chain is additionally introduced thereto.
PCT Publication No. WO96/25498 and U.S. Pat. No. 5,618,698 have disclosed that the activities of hTPO and hEPO glycoproteins are increased by introducing with one or more sugar chains.
The present invention has disclosed a human interferon-beta mutein having increased or improved activity or ability by introducing with a sugar chain into human natural interferon-beta, as a point of view described above.
Accordingly, in an embodiment of the present invention, there is provided a human interferon-beta mutein having increased or improved activity or ability by introducing a sugar chain into human natural interferon-beta.
Other objects or embodiments according to the present invention are provided hereunder.